Triggered sacral neuromodulation to treat neurogenic detrusor overactivity based on algorithmic classification of bladder filling status from wireless pressure data.

脊髓损伤或紊乱(SCI/D)引起的神经源性逼尿肌过度活动(NDO)影响80%的 患有脊髓损伤/D的个体也与帕金森氏症等周围神经退行性疾病有关。 疾病、多发性硬化症、糖尿病神经病变或中风。NDO会导致严重的尿失禁 影响有尊严、独立的生活，与许多合并症和跌倒风险相关联，是领先的 老年人功能衰退的因素。尿失禁会导致社会隔离和临床 退伍军人的抑郁与服兵役和创伤后应激障碍有关。 恢复尿液储存一直是NDO患者的首要任务。连续SNM为 一种非标签治疗，对一些患有NDO的人有效。触发的骶骨神经调节传入 哪种SNM仅在发生NDO的膀胱充盈周期中应用-可能会显示独特 在一些个人的治疗中受益。虽然触发的SNM增加了绵羊和大鼠的膀胱容量， 可行性还没有在患有NDO的人类身上得到证实。 这项研究的主要目标是论证增加膀胱容量和 使用触发式SNM降低退伍军人NDO患者的膀胱充盈压力这将在Unique基础上扩展 我们团队开发的技术：UroMonitor、上下文感知阈值(CAT)算法和 专用控制单元(ASCU)。UroMonitor是一种经尿道插入的小型传感器， 无线传输膀胱压力数据。CAT是一种基于小波的算法，可以检测逼尿肌 实时根据压力数据进行收缩。ASCU是一个模块化神经刺激平台，支持 无线通信和定制控制软件。我们将修改和集成这些技术，以 论证了退伍军人自动触发SNM的可行性。第二个目标是使用 尿液监测仪，以确定膀胱容量，逼尿肌收缩速度和充盈压力 经皮SNM评估以确定永久性治疗前SNM治疗有效的个体 植入。这两个翻译目标都将通过两个特定目标(SA)来实现： SA1将决定在自然充盈过程中对条件触发的SNM的膀胱反应的变化 患有NDO的退伍军人在两周的骶骨神经调节评估阶段后的周期。在SA1a，我们将 将短程无线电和低功率算法处理器集成到ASCU中以触发经皮SNM 在算法控制下。在SA1b中，我们将开发并在工作台上验证分类算法，该算法能够 基于逼尿肌收缩的自适应检测触发SNM。在SA1c中，我们将应用触发的SNM 使用从UroMonitor传输到ASCU的数据。触发的SNM将在3点应用8小时 8名退伍军人在为期两周的经皮评估阶段的时间点。排尿量、排尿时间 比较空洞和逼尿肌收缩频率，以确定条件SNM的变化 在两个时间点的反应，并与基线进行比较。结果度量将从验证后的 问卷调查，以尿管为参照的膀胱压力，以及收集排尿。 SA2将决定膀胱容量、充盈压力和逼尿肌收缩频率的变化 自然充盈周期贯穿持续两周的骶骨神经调节评估。在SA2a，我们将 将自适应天线集成到UroMonitor中，并开发出一种适用于男性和女性的插入工具。SA2b将 论证使用UroMonitor来表征NDO症状(膀胱容量、充盈程度)的可行性 压力和逼尿肌收缩速度)在几个膀胱充盈/排空周期。八名退伍军人将 接受标准的、持续的经皮SNM治疗两周。NDO症状将使用 SNM前及连续SNM后1周和2周后进行尿液监测。症状量化的准确性 将与标准的基于导管的测试和有效的排尿行为问卷进行比较。

Neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or disorder (SCI/D) affects 80% of individuals with SCI/D. It is also associated with peripheral neurodegenerative conditions such as Parkinson’s disease, multiple sclerosis, diabetic neuropathy, or stroke. NDO causes urinary incontinence that profoundly impacts dignified, independent living, associates with numerous comorbidities and fall risk, and is a leading factor in functional decline among the elderly. Urinary incontinence contributes to social isolation and clinical depression and associates with military service and post-traumatic stress disorder in Veterans. Restoring urine storage is consistently cited as a high priority by individuals with NDO. Continuous SNM is an off-label treatment, which is effective for some individuals with NDO. Triggered sacral neuromodulation—in which SNM is applied only during the portion of the bladder fill cycle where NDO occurs—could show unique benefit in treatment in some individuals. While triggered SNM increased bladder capacity in sheep and rats, feasibility has not yet been demonstrated in humans with NDO. The primary goal of this research is to demonstrate the feasibility of increasing bladder capacity and reducing bladder filling pressures using triggered SNM in Veterans with NDO. This will expand on unique technologies developed by our team: the UroMonitor, the Context-Aware Threshold (CAT) algorithm, and the Application Specific Control Unit (ASCU). The UroMonitor is a small, transurethrally-inserted sensor that wirelessly transmits bladder pressure data. CAT is a wavelet-based algorithm that detects detrusor contractions from pressure data in real time. The ASCU is a modular neurostimulation platform supporting wireless communication and custom control software. We will modify and integrate these technologies to demonstrate the feasibility of automatically triggering SNM in Veterans. A secondary goal is to use the UroMonitor to determine bladder capacity, detrusor contraction rate, and filling pressures during a percutaneous SNM evaluation to identify individuals who respond to SNM therapy before a permanent implantation. Both translational goals will be accomplished through two Specific Aims (SA): SA1 will determine the change in bladder response to conditionally-triggered SNM during natural filling cycles after a two-week sacral neuromodulation evaluation phase in Veterans with NDO. In SA1a we will integrate a short-range radio and low-power algorithm processor into the ASCU to trigger percutaneous SNM under algorithm control. In SA1b we will develop and bench-validate a classification algorithm capable of triggering SNM based on adaptive detection of detrusor contractions. In SA1c we will apply triggered SNM using data transmitted from the UroMonitor to the ASCU. Triggered SNM will be applied for eight hours at three timepoints in the two-week percutaneous evaluation phase in eight Veterans. Voided urine volume, time between voids, and detrusor contraction frequency will be compared to determine change in conditional SNM response at the two timepoints and compared to baseline. Outcome measures will be measured from validated questionnaires, catheter-referenced bladder pressures, and collected voided urine. SA2 will determine change in bladder capacity, filling pressure, and detrusor contraction frequency during natural filling cycles throughout a two-week continuous sacral neuromodulation evaluation. In SA2a we will integrate adaptive antennas into the UroMonitor and develop an insertion tool for men and women. SA2b will demonstrate the feasibility of using the UroMonitor to characterize NDO symptoms (bladder capacity, filling pressure, and detrusor contraction rate) over several bladder filling/emptying cycles. Eight Veterans will receive standard, continuous percutaneous SNM for two weeks. NDO symptoms will be measured using the UroMonitor before SNM and after one and two weeks of continuous SNM. Accuracy of symptom quantification will be compared to standard catheter-based testing and validated urinary behavior questionnaires.